Effects of metrifonate on escape and avoidance learning in young and aged rats.

The present study assessed the effects of the indirect acetylcholinesterase inhibitor metrifonate on learning and memory functions in young (3-month-old) and aged (25-month-old) rats. In the shuttle box, metrifonate at a dose of 12.5mg/kg, p.o., 30min before each of the daily acquisition sessions, improved the acquisition of the active avoidance response, whereas a dose of 25mg/kg did not. Metrifonate, 12.5mg/kg, p.o., administered before each of the daily acquisition sessions, also facilitated the acquisition of the Morris water escape task in both young and aged rats: metrifonate-treated rats swam a shorter distance to reach the escape platform than did the vehicle-treated rats. The 3-month-old rats treated with metrifonate did not show the increase in swimming speed over training observed in vehicle-treated animals; no effects of metrifonate were found on the swimming speed of aged rats. In a probe trial carried out immediately after the fifth daily acquisition session, metrifonate treatment did not affect the bias of the aged rats for the quadrant in which the platform had been positioned during acquisition. It is concluded that metrifonate improves performance during the acquisition phase of two aversively motivated learning and memory tasks at the dose of 12.5mg/kg, p.o.